Abstract

Background

Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized
from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity
and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism
in populations of European and Asian ancestry; no work has been done in populations
of African ancestry to date.

Results

In this study, we report that African Americans have significantly higher circulating
levels of plasma AA (p = 1.35 × 10-48) and lower DGLA levels (p = 9.80 × 10-11) than European Americans. Tests for association in N = 329 individuals across 80
nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure
of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10-16 in African Americans, 2.68 × 10-23 in European Americans). Ancestry-related differences were observed at an upstream
marker previously associated with AA levels (rs174537), wherein, 79-82% of African
Americans carry two copies of the G allele compared to only 42-45% of European Americans.
Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.

Conclusions

We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced
in African Americans due to the larger proportion of individuals carrying the genotype
associated with increased FADS1 enzymatic conversion of DGLA to AA.